6533b830fe1ef96bd1297a44
RESEARCH PRODUCT
Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism.
André BouchotAlexandra NicolasNicolas LarmonierDominique CathelinEric SolaryBernard BonnottePierre Emmanuel PuigJennifer FraszczakAndrew Batemansubject
Cytotoxicity ImmunologicLipopolysaccharidesT cellImmunologyBlotting WesternBone Marrow CellsBiologyNitric OxideImmune systemAdjuvants ImmunologicCell Line TumorNeoplasmsmedicineImmunology and AllergyCytotoxic T cellAnimalsHumansFollicular dendritic cellsCell DeathDendritic CellsFlow CytometryCell biologyRatsmedicine.anatomical_structureGranzymePerforinCell cultureApoptosisbiology.proteindescription
Abstract Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-γ-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-α, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-07-15 | Journal of immunology (Baltimore, Md. : 1950) |